SUBSTANCE: invention refers to medicine. There are described implanted devices with various versions of biologically active ingredient loading with the version selectable and applicable for creating a prolonged-release profile or a release profile having a low initial ejection of the biologically active ingredient from the implanted device.

EFFECT: there are described the implanted devices with various versions of biologically active ingredient loading.

11 cl, 2 dwg

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is based and has the advantage of priority of provisional application U.S. No. 61/244736, filed September 22, 2009, which is incorporated into this description in full by reference.

The LEVEL of TECHNOLOGY

In the field of pharmaceuticals there is a class of drugs for drug delivery that are designed to release biologically active components within the required time period after a single injection. Depot-medication - one of the names used to describe these drugs prolonged action. Depot preparations can be done in different ways. The usual approach to obtaining a depot of the drug or implant is to produce a solid matrix, which includes a biologically active component and inert polymeric filler. The purpose of the application of inert polymeric filler in the implant is the limitation of water inflow, which in turn regulates the dissolution of the biologically active component with subsequent release of biologically active component of the implanted matrix. In addition to physical and chemical properties of the biologically active component, the contribution to the rate of release of the biologically active component encodes the number of the biological�ski active ingredient in the implant.
That is, the increase in the number of biologically active component increases the speed of his release. Unfortunately, some implantable drugs require the presence inside the high number of biologically active component to have sufficient quantities of biologically active component capable to meet the requirements of dose and duration of action of the drug for specific medical conditions. However, the high amount of biologically active ingredient incorporated in the implant can cause too rapid release of the biologically active component, or the release of biologically active component may occur even with a fixed rate.

There is therefore a need for new implantable devices that can be downloaded in various forms, including high quantities of biologically active component, while still maintaining a satisfactory release profile, such as profile or prolonged release release profile with a low initial release including. These and other needs are met by using the present invention.

Summary of the INVENTION

Described implantable devices with different variants download to biologically active�mponent,
you can choose from and apply to create a predetermined release profile of a particular biologically active component of implantable devices.

Advantages of the invention will be partially set forth in the following description and will partly be obvious from the description or may be learned by practical implementation aspects described below. Following benefits will be realized and attained by the elements and combinations particularly listed in the attached claims. It should be understood that both the foregoing General description and the subsequent detailed description are only illustrative and explanatory and are not restrictive.

BRIEF description of the DRAWINGS

Fig. 1 shows a perspective view of the cross section of a typical implantable device comprising a core surrounded by a membrane sheath.

Fig. 2 shows a top view cross section of a device for co-extrusion, which can be used for the manufacture of implantable devices containing a nucleus surrounded by a membranous sheath.

DETAILED DESCRIPTION

Before describing and disclosing the present compounds, compositions, composites, articles, devices and/or methods should be understood that the aspects described below are not limited to specific �soedineniya,
compositions, composites, articles, devices, methods or applications, which, in fact, can, of course, vary. Also it should be understood that the terminology used here only serves the purpose of describing particular aspects of the invention and should not be considered limiting.

In this description and claims following, reference will be made to the number of terms for which you must specify the following values.

It will be understood that throughout the description, unless the context requires otherwise, the word "include" or variations such as "contains" or "containing", means including a specified number or stage or group of integers or steps but not to exclude any other number, or stage, or group of integers or steps.

It should be noted that used in the description and the attached claims, the singular form "a," "an" and "the" include numerous references, unless the context expressly otherwise requires. Thus, for example, reference to a "biologically active component" includes mixtures of two or more of such funds, etc.

The term "optional" or "optionally" means that the described event or circumstance may occur or may not occur and that the description includes all the examples in which the case or obstacles�in happen
and the examples that they don't happen.

In this document, the ranges can be labeled as "approximately" one particular value (and/or) until "approximately" another particular value. When such a range is indicated, another aspect includes the values from one specific value (and/or to the other particular value. Similarly, when values are expressed as approximate figures by applying the preceding words "approximately", it should be understood that the particular value forms another aspect. In addition, it should be understood that the limit values of each of the ranges are significant both in relation to the other limit value, and independently of the other limit value.

Mass percentage of a component, unless specifically stated otherwise, is calculated based on the total weight of the formulation or composition in which the component is turned on.

The term "disposable tool" refers to the agent, which is miscible with the polymer and is described subsequently be released from it, for example, as the destruction of the polymer.

The term "biologically active component" refers to a tool that has biological activity. The biologically active agent can be used for the treatment, diagnosis, treatment, pain relief, predopredelyayutsya (i.e., prophylactically),
enhance, modulate, or provide other beneficial effects on the disease, disorder, infection, etc. "Released biologically active component" refers to a biologically active component that can be extracted from the described polymer. Biologically active components also include those substances which affect the structure or function of the subject or a prodrug, which become biologically active or biologically active to a greater extent after it has been placed in a predetermined physiological environment.

Described compounds, compositions, and components that can be applied to obtain the drug, can be used in combination with the drug or can be used in drug represent the products of the described methods and compositions. Here describes these and other materials, and it should be understood that when described the combination, of a subgroup, interactions, groups, etc. of such materials, it is believed that each of these combinations specifically described here, despite the fact that while specific reference of each of various independent and joint combinations and the combination of these compounds may not be described explicitly. For example, if describes and discusses a number of different polymers and means, is expressly considered each of them and Luba� their combination and the combination of the polymer and the funds
unless specifically stated otherwise. Thus, if the described class of molecules A, B and C, as well as a class of molecules D, E and F, and described an example of a combination molecule, A-D, then even if each of the combinations of molecules are not listed individually, each is an individual and should be reviewed jointly. Thus, based on the description of A, B and C; D, E and F and the example combination A-D in this example was specifically addressed and should be considered describes each of the combinations A-E, A-F, B-D, B-E, B-F, C-D, C-E and C-F. similarly also specifically addressed and is considered to be described by any subgroup or combination of subgroups. Thus, for example, subgroup A-E, B-F and C-E was specifically addressed and should be described on the basis of the description of A, B and C; D, E and F; and the example combination A-D. This concept applies to all aspects of this invention, including, but not limited to, the stage of ways of making and using the described compositions. Thus, if there are various additional stages that can be carried out, it should be understood that each of these additional stages may be performed in any particular embodiment of the or combination of embodiments of the described methods, and that each such combination is specifically addressed and should be considered as described.

Usually the implant�trolled device according to the invention contain a longitudinal main part and the middle and far end (and the end surface on the near and far ends).
A longitudinal main part contains a biocompatible and/or biodegradable polymer. Longitudinal main portion contains a longitudinal surface of the core, which may involve: (i) partially or fully exposed surface, (ii) the surface is partially or completely covered with a biologically active component, (iii) the surface is partially or completely surrounded by (i.e., not open) polymer coating (which may contain or not contain a biologically active component and which surface can be coated with the biologically active ingredient or may not contain a biologically active component), or can be a combination of (i), (ii) and (iii).

Biologically active ingredient loaded into the implantable device in accordance with a specific embodiment of the load according to the desired release profile. By changing the boot option of biologically active component in the implantable devices according to the invention release profiles can be tailored to your specific needs and can provide complex release profiles.

Typically, biologically active component may be present in the implant (i.e., in the longitudinal main body and/or polymer membrane) or on any surface of the implant. Typically, biologically active component of mo�et: (i) be applied as a coating only on one or more end surfaces of the middle or the far ends,
(ii) be applied as a coating to one or more end surfaces near or far ends and only a portion of the outer surface of the longitudinal main portion or the entire outer surface of the longitudinal main part, (iii) be applied as a coating to a portion of the longitudinal main portion or all of the longitudinal main part, but not to cover both end surfaces, (iv) dissolve or dispergiermittel in the inner core (when present), (v) dissolve or dispergiermittel in a longitudinal main part, (vi) dissolving or dispergiermittel in the polymer shell (when present), (vii) be absent in the polymer shell (when present), or present any of the combinations (i) to(viii).

In one aspect of the invention, an implantable device may be loaded by volume. In this aspect of the invention, the biologically active component is dissolved or dispersed throughout the volume of the longitudinal main part. The surface of the implantable devices can be coated biologically active ingredient or may not contain a biologically active component. Such aspect may include examples in which the main longitudinal portion forms the inner core and surrounded by a polymer shell.

In another aspect of the invention a longitudinal main part contains�it inner core with a longitudinal surface of the core,
surrounded by a polymeric membrane, and exposed end surfaces of the middle and far ends, which are not surrounded by a polymer shell. The polymeric shell comprises a longitudinal outer surface, which is almost coextensive longitudinal surface of the core. The inner core contains a biodegradable polymer containing dissolved or dispersed therein a biologically active component. In one example of the polymer shell contains a biologically active component. In other examples, the polymer may contain dissolved or dispersed therein a biologically active component. For example, with reference to Fig. 1, the implantable device 100 includes a longitudinal main portion 130 containing the inner core 110, which is loaded with biologically active component, and the longitudinal surface of the core, which is surrounded by a polymer shell 150 and coextensive polymer sheath 150, which contains the outer surface of the polymeric shell 140. The implantable device also includes a coating 120 of a biologically active component on the end surfaces of the middle and/or far end, including a portion of the end surface formed by an outer polymeric sheath (but not inside a polymer shell), and a portion of the end surface formed by the inner core. In such in�the stage configuration of the invention the biologically active component can be applied as a coating on longitudinal surface in addition to the coating,
applied to the end surface. In yet another embodiment the bioactive component can be applied as a coating on the longitudinal surface and not to cover the near and far surfaces. In yet another embodiment the biologically active component may be present inside (i.e., in a dissolved or dispersed state) both in the core and polymer shell. In such an embodiment, the concentration of the drug in the core and the surrounding polymer shell may be the same or different.

In another aspect of the invention a longitudinal main part contains the inner core with a longitudinal surface of the core surrounded by a polymeric membrane, and exposed end surfaces of the middle and far ends, which are not surrounded by a polymer shell. The polymeric shell comprises an outer longitudinal surface, which is almost coextensive longitudinal surface of the core. The inner core contains a biodegradable polymer and does not contain a biologically active component or contains dissolved or dispersed therein a biologically active component. In this aspect, the bioactive component can be applied as a coating on one or more exterior surfaces, including one� or more longitudinal outer surfaces,
end surface at the near end, the end surface at the far end, or a combination, including those examples in which the biologically active component is applied to each part of the exposed surface of implantable devices or on all exposed surfaces of the implantable device.

In another aspect of the invention, an implantable device comprises a longitudinal main body, which may have a longitudinal surface that is surrounded or not surrounded by a polymeric membrane sheath and, thus, remains open. In this longitudinal aspect of the invention the main part of the dissolved or dispersed, and the biologically active component is present only on one or more end surfaces of the middle or the far end.

In one aspect of the invention, an implantable device having a definite order of arrangement of the core/shell can be obtained by the method comprising: a) forming a core of a desired shape from a mixture of biodegradable polymer and optionally a biologically active component (if you want to download the inner core); (b) forming a membranous sheath surrounding the core; c) exposure of the end faces in the near and far end by removing the portion of the membrane sheath that surrounds the end surface./p>

For option core/shell, in which the biologically active component is dissolved or dispersed in the inner core, the formation of the nucleus implantable devices can be achieved when the initial mixing at least one biodegradable polymer and at least one biologically active component to provide a mixture. Mixing a biodegradable polymer and a biologically active component can be done using methods known in the art. For example, the polymer and the biologically active component can be subjected to dry blending (i.e. mixing of the polymer particles and the component), for example, using a V-blender Patterson-Kelly or granulated prior stage of processing, i.e. before the formation of the nucleus of a desired shape. It is assumed that other components such as inert fillers, can be mixed with the polymer and biologically active component of the mixture before processing into the kernel.

Stage of mixing may include the use of solvent. However, in other aspects of the invention mixing a biodegradable polymer and a biologically active component does not include the use of solvent. If avoiding the use of solvent during mixing, you can implement a number of advantages. First of all�x,
the use of solvent during mixing requires an extra stage of processing for removal of the solvent. Secondly, if the delivery system is implanted in the subject, the selected solvent must be biocompatible, should any residual solvent remains in the device. The solvent can adversely affect the morphology of the delivery system in General, which can lead to the unwanted release scheme. The solvent may adversely affect the stability of the biologically active component during the manufacturing process. Finally, the level of the solvent requires monitoring, since it needs to be low enough to meet regulatory guidelines.

Processing the mixture in the inner core can be made in these conditions to the biologically active component is uniformly mixed, dispersed or dissolved in the polymer or only in certain portions of the polymer. Of the compounds can be produced inner core of a desired shape by various methods, such as melt extrusion, injection molding, compression molding or compressing the mixture on a roller press to obtain a desired shape or structure. Methods of production using extrusion, may include, but not limi�cuautla tabletting.
Depending on the conditions of processing of biodegradable polymer used as starting material at the stage of mixing may be the same polymer that is present in the target device, or may be a different polymer. For example, the polymer during processing (in the core) may be subjected to reactions of polymerization or depolymerization, which eventually can lead to polymer different from the polymer, which was used until the beginning of the processing (in the core). Thus, used here, the term "polymer" comprising a biologically compatible polymer and a biodegradable polymer that covers the polymers used as starting materials and the final polymer in a target device.

In one aspect of the invention will first do the inner core of desired shape, as discussed above (with the biologically active component), and then form a membrane envelope that surrounds the nucleus. In other aspects of the invention discussed below, the inner core and membrane shell can be done together, for example, using co-extrusion, while providing an implantable device. When first formed the inner core, membrane shell in the future, you can generate application�m ways
known in the art. In one aspect of the invention, the membrane shell can be formed on the inner core by applying a polymer by spraying or by coating by dipping in a solution containing a biocompatible polymer (and optionally a biologically active component). In this aspect of the invention, the membrane shell can be formed around the entire inner core so that the inner core had the exposed surface. After the formation of the membrane membrane part of the membrane sheath can be removed, for example, by dissolving or cutting the physical part of the membrane of the shell to provide an open surface of the inner core (i.e., the end surface of the near or far end). In other aspects of the invention membrane shell can be formed by surrounding only part of the kernel so that after the formation of the membranous sheath the core contained an open surface.

In another aspect of the invention, an implantable device can be obtained by co-extrusion, for example, by the method comprising: a) extruding a biodegradable polymer, or alternatively a mixture of a biodegradable polymer and a biologically active component, through the inner coaxial injection hole forming�tion of the kernel;
(b) forming a continuous composite workpiece by simultaneous extrusion of biocompatible polymer, or alternatively a mixture of a biocompatible polymer and a biologically active component, through the outer coaxial injection hole for the application of producing specific coextensive strings almost membranous sheath surrounding the core; C) cutting the continuous composite billet from step (b) to one or more of the bars containing the longitudinal surface and two end surfaces. For example, this way you can receive implantable device shown in Fig. 1.

With reference to Fig. 2 the method of co-extrusion can be performed using different devices for co-extrusion, is known in the art. Fig. 2 shows a cross-section 60 of this device. In the method of co-extruding the polymer mixture, which can be formed, as discussed above, flows through the inner coaxial injection hole 65, while biologically compatible polymer or compound, from which to generate membrane shell, flows through the outer coaxial injection hole 60. Internal 65 60 and outer coaxial nozzle then narrowed on the sections of the mold 68 and 70, where the biologically compatible� polymer or mixture of biodegradable polymer or mixture of biodegradable polymer/biologically active components are integrated and take the desired shape of the implantable device
which in this example is a cylinder. Then continuous composite preform obtained by joint extrusion, leaves the device at the point of exit 80. After co-extrusion of a continuous composite preform obtained by joint extrusion, can be cut into one or more bars containing a longitudinal surface and two end surfaces, as discussed above and as shown in Fig. 1. Thus, after cutting of the continuous workpiece, obtained by joint extrusion, it is possible to form the implantable device by cutting a continuous workpiece into separate blocks, each of which contains a longitudinal surface and end surface in the near and the far ends, as discussed above. Continuous billet can be cut into as many bars as needed to get the desired number of implantable devices or implantable devices desired longitudinal length.

Implantable devices that do not have a specific order of arrangement of the core/shell can be obtained by using more simple extrusion methods, for example with the use of extrusion with the use of simple molds and cutting the workpiece on one or more bars, as discussed above.

Implantable devices in some aspects of the invention, the soda�RATM coating of a biologically active component on one or more surfaces of the device.
The coating of the biologically active component can be applied to the implantable device by preparing the corresponding solution of the dispersion of the biologically active component in a solvent and then coating the resulting solution on one or more exposed surfaces of the implantable device. The coating solution can be done by spraying, dipping, coating the solution with a brush, etc. to the desired surface of implantable devices, with the possibility of evaporation of the solvent, if required.

Biodegradable polymer that forms the inner core or membrane shell (when present), may include any of the biodegradable polymers listed above, or any other biodegradable polymer known in the art. In an additional aspect of the invention biocompatible and/or biodegradable polymer can be a poly(lactide), poly(glycolide), a copolymer of lactide with glycolide, poly(caprolactone), a complex of poly(Ortofon), poly(FD�phase),
poly(hydroxybutyrate) or a copolymer containing poly(hydroxybutyrate), a copolymer of lactide and caprolactone, polycarbonate, complex polyetherimide, polyanhydride, poly(dioxanone), poly(alkalinuria), a copolymer of polyethylene glycol and complex polyarteritis, biodegradable polyurethane, a poly(amino acid), polyamide, complex polyetherimide, a polyester-ether copolymer, Polyacetal, a polycyanoacrylate, a copolymer of poly(oxyethylene)/poly(oxypropylene), Polyacetal, policital, complex polyphosphatase, polyhydroxyvalerate or copolymer containing polyhydroxyvalerate, polyalkylacrylate, polyalkylacrylate, poly(maleic acid) and their copolymers, terpolymers, combinations, or mixtures thereof.

In yet another additional aspect of the invention is applicable biodegradable and biocompatible polymers are polymers that contain one or more residues of lactic acid, glycolic acid, lactide, glycolide, caprolactone, hydroxybutyrate, hydroxyvalerate, dioxanone, polyethylene glycol (PEG), polyethylene oxide, or a combination. In yet another additional aspect of the invention is applicable biodegradable polymers are polymers that contain one or more residues of lactide, glycolide, caprolactone or a combination thereof.

In one aspect of the invention�Enimie biodegradable and biocompatible polymers are polymers
which contain one or more blocks of hydrophilic or water-soluble polymers, including but not limited to, polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP) in combination with one or more blocks of other biocompatible or biodegradable polymer, which contains a lactide, glycolide, caprolactone or a combination thereof.

In particular aspects of the invention are biodegradable and/or biocompatible polymer may contain one or more lactide residues. In this regard, the polymer may contain any lacheny residue, including all racemic and stereospecific forms of lactide, including, but not limited to, L-lactide, D-lactide and D,L-lactide or a mixture thereof. Applicable polymers containing a lactide, include, but are not limited to, poly(L-lactide), poly(D-lactide) and poly(DL-lactide); and a copolymer of lactide with glycolide, including a copolymer of L-lactide with glycolide, a copolymer of D-lactide with glycolide copolymer of DL-lactide with glycolide; or copolymers, terpolymers, combinations, or mixtures thereof. A lactide/glycolide polymers can be conveniently obtained by polymerization in the melt via ring-opening of lactides and glycolide monomers. In addition, racemic polymers of DL-lactide, L-lactide and D-lactide are commercially available. L-polymers are more Krista�chip metallic and are absorbed more slowly
than DL-polymers. In addition to the copolymers containing glycolide, DL-lactide or L-lactide, copolymers of L-lactide and DL-lactide are commercially available. The homopolymers of lactide or glycolide are also commercially available.

When biodegradable and/or biocompatible polymer is a copolymer of lactide with glycolide, poly(lactide), or poly(glycolide), the amount of lactide and glycolide in the polymer can vary. In an additional aspect of the invention, the biodegradable polymer contains from 0 to 100 mol.%, from 40 to 100 mol.%, from 50 to 100 mol.%, from 60 to 100 mol.%, from 70 to 100 mol.% or from 80 to 100 mol.% lactide and from 0 to 100 mol.%, from 0 to 60 mol.%, from 10 to 40 mol.%, from 20 to 40 mol.% or from 30 to 40 mol.% glycolide where the amount of lactide and glycolide is 100 mol.%. In an additional aspect of the invention, the biodegradable polymer can be a poly(lactide), lactide copolymer with glycolide in the ratio 95:5 copolymer of lactide with glycolide in the ratio 85:15 lactide copolymer with glycolide in the ratio of 75:25 lactide copolymer with glycolide in the ratio 65:35, or a copolymer of lactide with glycolide in the ratio of 50:50, where the relationships represent a molar ratio.

In an additional aspect of the invention, a biodegradable and/or biocompatible polymer can be a poly(caprolactone) or a copolymer of lactide with caprolactone. In one aspect�in the invention, the polymer may be a copolymer of lactide with caprolactone,
which in various aspects of the invention may be a copolymer of lactide with caprolactone in a ratio of 95:5 copolymer of lactide with caprolactone in a ratio of 85:15, a copolymer of lactide with caprolactone in a ratio of 75:25, a copolymer of lactide with caprolactone in a ratio of 65:35, or a copolymer of lactide with caprolactone in a ratio of 50:50, where the relationships represent a molar ratio.

When either biodegradable or biocompatible polymers include polymers based on lactitol, polymers on the basis of lactitol can contain any lacheny residue, including all racemic and stereospecific forms of lactitol, including, but not limited to, L-lactide, D-lactide and D,L-lactide, or a mixture thereof. Applicable polymers containing a lactide, include, but are not limited to, poly(L-lactide), poly(D-lactide) and poly(DL-lactide); and a copolymer of lactide with glycolide, including a copolymer of L-lactide with glycolide, a copolymer of D-lactide with glycolide copolymer of DL-lactide with glycolide; or their copolymers, terpolymers, combinations thereof, or mixtures thereof. A lactide/glycolide polymers can be obtained by opening the ring lactide and glycolide monomers. In addition, racemic DL-lactide, L-lactide and D-lactide polymers are commercially available. L-polymers are more crystalline and absorbed more slow�NGOs,
than DL-polymers. In addition to the copolymers containing glycolide, DL-lactide or L-lactide, copolymers of L-lactide and DL-lactide are commercially available. The homopolymers of lactide or glycolide are also commercially available.

The biodegradable polymer can be destroyed and thus gives the opportunity to release the agent from the inner core of the implantable device. In the compositions can be applied to various funds released. You can typically use any tool for which it is desirable gradual release. Thus, the redundant remedy can be a biologically active component, a cosmetic substance, such as liquid cosmetic, or other substance, such as an agricultural product. The released drug can be dissolved or dispergiermittel in the polymer and may be present in any suitable amount, which usually will depend on the intended application of the composition.

With implantable devices can be applied a number of biologically active components. The biologically active component can be blended, mixed or otherwise combined with biodegradable polymer of the inner core, membrane shell and/or applied as a coating on one or several surfaces, as discussed above. In one aspect of the invention, and biologically�tive component can be pre-mixed with sugar,
for example to dry when sprayed with sugar to form a certain particle. In another aspect of the invention, at least a portion of the biologically active component can be dissolved in the biodegradable polymer. In an additional aspect of the invention, at least a portion of the biologically active component can be dispersed in the biodegradable polymer of the inner core and/or membrane shell (when it is present).

Mixing the biologically active compound and polymer can be carried out with additional solvent (different from the polymer) or without, as discussed above. The amount of biologically active ingredient included in the composition varies depending on the particular drug, the desired therapeutic effects and the required duration of exposure. It is believed that because of different composition to provide regimens medicines for different purposes of therapy, there is no standardized high or low limit on the number of medicines included in the composition. The lower limit will generally depend on the activity of the drug and duration of its release from the device. Specialists in pharmaceutical fields can determine toxic levels of l�drug funds
as well as the minimum effective dose.

You can apply different forms of the biologically active component that is able to free himself from implantable devices in the body of the subject. In the device described here can be incorporated in liquid or solid bioactive component. Biologically active components may be water soluble or water insoluble. In some aspects of the invention, the biologically active component, at least very slightly soluble in water and is preferably moderately water-soluble. Biologically active components may include salts of the active ingredient. In this regard, biologically active components may be acidic, basic or amphoteric salt. They may represent a non-ionic molecules, polar molecules, or molecular complexes capable of forming hydrogen bonds. The biologically active component can be included in devices, such as uncharged molecules, molecular complex, a salt, ether, ester, amide, the polymer conjugate is a drug or other form to provide the effective biological or physiological activity.

In some aspects of the invention the device itself �can be a carrier and/or may be combined with other carriers or additives.
You can also apply other pharmaceutical carriers. Examples of solid carriers, different from the polymer (if it is solid), include lactose, calcium sulfate, sucrose, talc, gelatin, agar, pectin, gum, magnesium stearate, and stearic acid. Examples of liquid carriers different from the polymer (if it is liquid), are sugar syrup, peanut oil, olive oil and water. Examples of gaseous carriers include carbon dioxide and nitrogen. Other pharmaceutically acceptable carriers or components that can be mixed with biologically active ingredient, can include, for example, fatty acid, sugar or salt.

In one aspect of the invention, the composition may be in the set. The kit can contain a suitable box or container for the compositions. Examples include, without limitation, sterile packaging. Since such compositions are suitable for use as compositions for injection, the kit can include a pre-packaged device for injection containing a device for injection that contains an implantable device. A suitable device for injection include, without limitation, syringes, trocars, and other devices.

As discussed above, implanted devices can be used d�I deliver the biologically active substance to a subject,
who needs treatment, for example, for the treatment of disorders, for the treatment which can be effective is the use of biologically active component. The songs can be entered in any tissue or fluid of the subject. Similarly, the method of administration can be any suitable method, such as subcutaneous injection, oral administration, parenteral administration, enteral (abdominal) introduction, etc. In some aspects of the invention liquid compositions containing one or more polymers of low viscosity, you can enter the subject in the form of an injection. The nature of composition administered will typically be selected based on the desired dosage of biologically active component, which will greatly vary depending on the disorder, but can easily be determined by a specialist in pharmaceutical fields.

"Effective amount" of a composition refers to the amount of the composition to provide the desired therapeutic result. Thus, an effective amount will vary significantly depending on the composition, the biologically active component and a disorder or condition that requires treatment. In fact, an effective amount and dosage of the drug composition introduced to the subject, you can determine with the physical and physiological factors that�them as body weight,
the severity of the condition, the type of disease being treated, previous or concurrent therapeutic interventions, idiopathy patient, and may depend on the method of administration. Depending on dosage and method of administration the number of reference preferred dosage and/or an effective amount may vary in accordance with the response of the subject. An effective amount of the described pharmaceutical composition can be determined by a specialist in this field.

In some non-limiting examples, a dose may contain from about 1 microgram/kg body weight to about 5 micrograms/kg of body weight, up to about 10 micrograms/kg body weight, about 50 microgram/kg body weight, about 100 microgram/kg of body weight, about 200 microgram/kg body weight, about 350 microgram/kg / body weight, about 500 microgram/kg body weight, about 1 milligram/kg / body weight, about 5 milligram/kg body weight, up to about 10 milligram/kg / body weight, about 50 milligram/kg / body weight, about 100 milligram/kg / body weight, about 200 milligram/kg / body weight, about 350 milligram/kg / body weight, about 500 milligram/kg of body weight to about 1000 mg/kg of body weight ilible per the introduction comes at any range,
obtained in these ranges. In non-limiting examples, the dose can be entered in any of the received range from the numbers listed here, in the range from about 5 mg/kg body weight to about 100 mg/kg body weight, about 5 microgram/kg of body weight to about 500 milligram/kg / body weight, etc. based on the numbers described above.

The biologically active component may be present in the implantable device at any suitable mass percent, including the introduction of higher mass percent, such as the introduction of up to 40 wt.% in the calculation of the mass of the implantable device or weight devices. In one aspect of the invention, the implantable devices can be used for modifying the pharmacokinetics of biologically active component.

Compositions containing implantable devices, you can enter any desired subject. The subject can be a vertebrate animal, such as mammal, fish, bird, reptile or amphibian. The subject for the methods described herein can be, for example, human, Primate, non-human, horse, pig, rabbit, dog, sheep, goat, cow, cat, Guinea pig or rodent. Conditions do not account for the specific age or gender. Thus, it is assumed that the invention covers adults and novolog�military subjects,
as well as fetuses, whether male or female. The compositions can also be entered by any suitable means, including parenteral, oral method, including. In one preferred aspect of the invention, the composition can be led to the subject by injection.

It is possible to make various modifications and variations described here, compounds, composites, kits, articles, devices, compositions, and methods. Other aspects described herein of the compounds, composites, kits, articles, devices, compositions and methods will be apparent from the description and the practical implementation described here, compounds, composites, kits, articles, devices, compositions, and methods. It is believed that the description and examples should be considered illustrative.

1. An implantable device comprising a longitudinal main body, having an inner core containing the longitudinal surface surrounded by a polymer shell, and the open end surface on the near and far ends, which are not surrounded by a polymeric shell;in which the polymeric shell comprises a longitudinal outer surface, which is almost coextensive the longitudinal surface of the inner core;in which at least the inner core or polymeric shell comprises a biodegradable polymer;in which both the inner core and p�limera sheath containing dissolved or dispersed in a biologically active component;
andin which the inner core and polymer shell have corresponding concentration of the biologically active component, wherein the concentration of the biologically active component in a polymer shell that differs from the concentration of biologically active ingredient in the inner core; andthe biologically active component of the inner core and polymer shell is present in the implantable device to 40% based on the weight of implantable devices.

2. Implantable device according to claim 1, wherein one or more end surfaces at the near end, the far end or on the longitudinal outer surface coating of a biocompatible or biodegradable polymer.

3. Implantable device according to claim 1, wherein one or more end surfaces at the near end, the far end or on the longitudinal outer surface is applied as a coating of a biologically active component, which is the same or different from the biologically active component is dissolved or dispersed in the inner core and/or polymer membrane shell.

4. Implantable device according to claim 1, wherein the polymeric shell comprises a polymer that forms a protective membrane around the inner core.

5. Implantable device according to claim 1, in which� inner core longitudinal main part contains poly(lactide),
poly(glycolide), poly(caprolactone), copolymers of lactide with glycolide or a mixture thereof, a combination or copolymer.

6. Implantable device according to claim 1, wherein the polymeric shell longitudinal main part contains poly(lactide), poly(glycolide), poly(caprolactone), copolymers of lactide with glycolide or a mixture thereof, a combination or copolymer.

7. Implantable device according to claim 1, wherein both the inner core and the polymer shell contains a biodegradable polymer.

8. Implantable device according to claim 7, in which both the inner core and polymer shell longitudinal main parts contain poly(lactide), poly(glycolide), poly(caprolactone), copolymers of lactide with glycolide or a mixture thereof, a combination or copolymer.

SUBSTANCE: what is described is a mesh bioactive wound coating with its base containing disintegrated bacterial cellulose comprising antimicrobial and antioxidant ingredients: silver-modified montmorillonite and fellerenol aiming at optimising the course of the wound process, preventing the development and suppression of a wound infection. The mesh bioactive wound coating is used for treating gunshot wounds, severe mechanical injuries, uninfected and infected wounds, including septic and persistent wounds, granulating wounds following deep thermal, chemical and radiation burns, for conducting the integrated treatment of trophic ulcers and bedsores in hospital, out-patient and field settings.

EFFECT: mesh bioactive wound coating is non-toxic; it causes no local irritant and skin re-absorption action, possesses elasticity, a high degree of wound modelling; it is not fragmented that facilitates a wound care.

SUBSTANCE: invention relates to compositions for local application for the prevention and treatment of local eye pathologies, in particular inflammatory keratites and conjunctivitis and the dry eye syndrome, which contain as active ingredients polyunsaturated fatty acids of the omega-3 and omega-6 type, namely, EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid) and GLA (γ-linolenic acid), mixed with vitamin E acetate and combined into a stable composition in a hydrogel, that is in the disperse form in a water solution, containing one or more gel-forming polymers. The claimed compositions are especially recommended for application as artificial tears.

EFFECT: invention provides an increased efficiency of the prevention and treatment of eye pathologies.

SUBSTANCE: what is described is a medical semisynthetic biological adhesive based on biopolymer nanocomposites as a semisynthetic polymer matrix containing a substrate presented by low-molecular polyisobutylene, collapan as an excipient, human immunoglobulin, castor aerosol lubricant as a binding agent; faster setting of the microporous sandwich adhesive is ensured by performing an operation by means of a repetitively pulsed laser (CO2 laser) scalpel in a combination with a semiconductor laser. A polyacrylamide hydrogel placed into a polymer bath is used as a setting agent of an upper layer that is a polymer plaster tape.

SUBSTANCE: what is described is a gel containing structured nanovesicles - niosomes prepared from silicone compounds with enclosed albendazole, anthelmintic preparation.

EFFECT: invention enables extending the range of application of the anthelmintic preparations by reducing dyspeptic reactions that makes them applicable in both adults, and children suffering gastrointestinal diseases.

SUBSTANCE: invention provides a method of encapsulating antiseptic-stimulator Dorogova (ASD) fraction 2. The method is a physical-chemical non-solvent deposition method. When carrying out the method, the cladding of the microcapsules used is sodium alginate and the precipitation agent is carbon tetrachloride.

SUBSTANCE: group of inventions refers to medicine, namely to ophthalmology, and aims at treating eye discomfort. Treating the eye discomfort is ensured by applying a liquid composition containing a cooling agent. The cooling agent represents 2,3-dihydroxypropyl ester of (1R,2S,5R)-2-isopropyl-5-methylcyclohexane carboxylic acid (or CPS-030). The liquid composition of the cooling agent is applied locally on at least a part of the outer surface of the eyelid (preferentially a closed one) to be treated. Preferentially, the liquid composition of the cooling agent is applied on a tissue, a tampon or a wipe or is enclosed into a tissue, a tampon or a wipe, e.g. an eye wipe.

EFFECT: using the group of inventions provides the prolonged relief of the eye discomfort with no eye irritation.

SUBSTANCE: invention refers to medicine, specifically to pharmaceutical compositions possessing prolonged antiarrhythmic actions and applicable to correct the cardiac arrhythmia, including that of the ischemic origin. What is presented is a pharmaceutical composition with the prolonged antiarrhythmic acitivity containing bis[2-(diethylamino)]-N-(2,6-dimethylphenyl)acetamide L-glutaminate, L-glutamic acid, 2-aminoethane sulpho-acid and excipients.

EFFECT: prolonged antiarrhythmic action and stability of the dosage form (tablets, capsules for oral application or solution for injections).

SUBSTANCE: invention represents a biologically active composition in the form of an orally dispersible tablet characterised by the fact that its contains dehydroepiandrosterone (DHEA) as an active ingredient and inert excipients: mannitol, sorbitol, manitol, crospovidone, copovidone, a lubricant, an intensive sweetener and a flavouring agent in certain proportions.

EFFECT: invention provides the new form of the biologically active additive of dehydroepiandrosterone.

SUBSTANCE: invention relates to field of microcapsulation, in particular to method of obtaining microcapsules of medications of cephalosporin group. Method is characterised by the fact that as envelope of microcapsules applied is poludanum, powder of medication of cephalosporin group is added to poludanum water solution in presence of surface-active substance E 472c, ratio of poludanum amount and medication of cephalosporin group in counted per dry substance constitutes 3:1, obtained mixture is mixed to complete dissolution of reaction mixture components and carbinol is added drop-by-drop as first precipitator, and then diethyl ether is added as second precipitator, obtained suspension of microcapsules is filtered, washed by acetone, and dried in exsiccator.

EFFECT: method ensures simplification and acceleration of process of obtaining microcapsules of water-soluble medications of cephalosporin group in poludanum, reduction of loss in the process of obtaining microcapsules.

SUBSTANCE: invention relates to microencapsulation, particularly to a method of producing zinc oxide microcapsules. The method is characterised by that the microcapsule shell used is carrageenan, wherein a weighed portion of zinc oxide in dimethylsulphoxide is mixed with a suspension of carrageenan in butanol in the presence of an E472c surfactant; ethanol is added to the obtained suspension as a precipitant; the obtained suspension is filtered and dried at room temperature.

SUBSTANCE: sodium carboxymethylcellulose is used as coating for microcapsules. Charge of fenbendazole, dissolved in dioxane, or dimethylsulphoxide, or dimethylformamide, is dispersed into solution of sodium carboxymethylcellulose in cyclohexanol in presence of surface-active substance E472c, mixing is performed at 1000 rev/s. Weight ratio of fenbendazole and sodium carboxymethylcellulose constitutes 1:3 respectively, after which mixture of butanol and distilled water taken in volume ratio 2:1 respectively is added, obtained suspension of microcapsules is filtered and dried. The process of obtaining fenbendazole microcapsules is realised at 25°C.

EFFECT: simplification and acceleration of the process of obtaining fenbendazole microcapsules in carboxymethylcellulose, reduction of loss in the process of obtaining microcapsules.

SUBSTANCE: invention represents a pharmaceutical composition for treating the HIV infection in the form of a solid dosage form, containing at least one HIV protease inhibitor in a therapeutically effective amount specified in a group of nelfinavir, sacvinavir, tipranavir, darunavir, indinavir, ritonavir, lopinavir, palinavir or fosamprenavir, and pharmaceutically acceptable additives differing by the fact that as the pharmaceutically acceptable additives it contains at least one water-insoluble polymer from 0.39 to 28 wt % of the total dosage form, surfactants, excipients up to 100% of the total dosage form, as well as a method of treating the HIV infection.

EFFECT: pharmaceutical composition according to the invention possesses the improved technological properties and improved bioavailability as compared to a prototype therapeutic agent.

SUBSTANCE: invention refers to medicine, particularly to a method for active substance (AS) delivery through an epidermal barrier. The declared method involves using a matrix-type transdermal patch containing a substrate, a protective tape and a polymer layer, and characterised by the fact that 10% PEG-12 dimethicone niosomes are introduced into the polymer layer of the transdermal patch; then the substrate is coated with the polymer layer. The ACs are encapsulated into the niosomes with the use of hemogeniser APV, as well as 10 wt % propylene glycol and 5 wt % isopropyl myristate.

SUBSTANCE: invention refers to medicine and cosmetology and can be used for the effective transdermal delivery of the wide range of active substances (AS). What is declared is a method for the transdermal delivery of the active substances as a part of PEG-12 dimethicone niosomes characterised by the fact that the AS are included into the niosomes in the concentration of 10% by homogenising gel containing 10% niosomes in the homogeniser APV.

EFFECT: invention provides the higher transdermal effect of the interstitial delivery of the AS as a part of the niosomes.

SUBSTANCE: group of inventions refers to pharmaceutics and medicine, and concerns protein and peptide stabilisation formulation which contains a hydrophilic polymer, a mixture of polyalcohol and sugar, wherein a weight ratio of polyalcohol to sugar makes from 2:1 to 5:1 (wt %), a detergent, and wherein the formulation is free from stabilising proteins. A composition and a kit for treating a disease or a composition caused by hyperactive cholinergic innervation of muscles or endocrine glands in a patient, and contain the above formulation and peptide, protein or a mixture thereof.

EFFECT: group of inventions provides the better protein stability in the absence of stabilising proteins.

SUBSTANCE: invention refers to medical equipment, namely to stents representing intraluminal prostheses implanted into body vessels, e.g. blood vessels, for supporting and keeping the vessels closed and for fixing and holding other prostheses in the vessels. The stent comprises a basic coiled stent component and a brace holding the coiled structure of the basic stent component. The basic stent component comprises a first rough side edge, a second rough side edge, a first end edge and a second end edge. The first side edge is connected to the second side edge. Each of the end edges is wavelike-contoured and comprises straight cylinders on long ends of the stent. According to the first embodiment of the basic stent component, the first end edge has irregularities, first and second edges, connected to the first side edge and inclined at an oblique angle thereto. According to the second embodiment of the basic stent component, the first side edge has irregularities connected to the first end edge having irregularities. The first end edge extends at an oblique angle towards the above first side edge. The first side and first end edges has a wavelike contour braced cross bars. At least one bar has a cell structure, while a width of the above braces is less than a width of at least one bar containing the cell structure. A method for providing the basic stent component according to the first and second embodiments consists in coiling the basic stent component along the long axis and closing the first end of the first end edge with the second edge of the first end edge for forming the straight cylinder in relation to the long axis of the stent.

EFFECT: stent has a good radial strength and a high degree of longitudinal flexibility, while a making process is simple and low-cost with no increase of manufacturing defects.